EP3661586A1 - Système d'application contenant une matrice de micro-aiguilles présentant un principe actif pour la cicatrisation - Google Patents

Système d'application contenant une matrice de micro-aiguilles présentant un principe actif pour la cicatrisation

Info

Publication number
EP3661586A1
EP3661586A1 EP18759262.1A EP18759262A EP3661586A1 EP 3661586 A1 EP3661586 A1 EP 3661586A1 EP 18759262 A EP18759262 A EP 18759262A EP 3661586 A1 EP3661586 A1 EP 3661586A1
Authority
EP
European Patent Office
Prior art keywords
microneedle array
applicator system
active ingredient
oil
wound healing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP18759262.1A
Other languages
German (de)
English (en)
Inventor
Stefan Henke
Karsten Heuser
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LTS Lohmann Therapie Systeme AG
Original Assignee
LTS Lohmann Therapie Systeme AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LTS Lohmann Therapie Systeme AG filed Critical LTS Lohmann Therapie Systeme AG
Publication of EP3661586A1 publication Critical patent/EP3661586A1/fr
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/164Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/17Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728Hyaluronic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/63Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/886Aloeaceae (Aloe family), e.g. aloe vera
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023Drug applicators using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046Solid microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0061Methods for using microneedles

Definitions

  • Applicator system comprising a microneedle array having a drug for wound healing
  • the invention relates to an applicator system containing a microneedle array and its use for the intradermal administration of active substances, in particular medicaments, this microneedle array being suitable for skin penetration on humans or animals and comprising at least one active ingredient for wound healing.
  • microneedle systems and devices in which microneedle arrays are used for the painless intradermal (or transdermal) administration of substances, in particular drugs, are known in the art. Nevertheless, there is a great need to promote wound healing.
  • the skin consists of several layers.
  • the outermost skin layer, the stratum corneum has known barrier properties to prevent foreign substances from entering the body and exiting the body from the body.
  • the stratum corneum which is a complex structure of compacted keratotic cell debris approximately 10-30 microns thick, forms a watertight membrane to protect the body. This natural impermeability of the stratum corneum prevents administration of most pharmaceuticals and other substances through the skin as part of an intradermal application.
  • the administration of various substances therefore takes place, for example, by producing micropores or sections in the stratum corneum and supplying or applying a drug into or under the stratum corneum.
  • numerous drugs e.g. also administered subcutaneously or intradermally or intracutaneously.
  • applicator systems are used to apply a microneedle array under pressure on the skin and lead to a sudden stress on the skin.
  • the strong brief pressure load on the skin can lead to additional irritation as well as to micro-lesions even (micro-) skin cracks. This problem can be accompanied by the symptom of a strong itching with skin redness and skin swelling.
  • an applicator system containing a microneedle array for the intradermal administration of drugs in particular drugs to promote wound healing with and after the application and a prevention of negative consequences, such as itching, swelling, skin irritation, redness, blisters, bleeding and inflammation Afford.
  • the invention relates to such in particular with the features of claim 1, namely an applicator system comprising a microneedle array for use in the intradermal application of a first active ingredient comprising a plurality of microneedles on a carrier, wherein the microneedles and / or the carrier at least one second active ingredient for wound healing.
  • such suitable active ingredients for wound healing are selected from the group consisting of absinthe, algae extract, allantoin, allantoinum, alliumcepae, aloe vera, aluminum acetate, ammonium bituminosulphonate, pineapple extract, apricot kernel arganol, arnica, eye rust extract, bamboo extract, benzalkonium chloride, benzethonium chloride, beta carotene, beeswax, henbane oil , Bismuth, broccoli seed, calendula, cetylpyridinium chloride, chondroitin, citronella, caffeine, collagen, cupuacubutter, dexpanthenol, dextrocamphora, guaiac wood, pomegranate extract hamamelis bark, hemodialysates, urea, helianthus oil, hyaluronic acid, jojobaol, chamomile flowers, kaolin, poppy, larch
  • the active ingredients for wound healing may be incorporated in a formulation with customary auxiliaries and additives, in particular in a liquid or gel.
  • the first active substance such as a drug
  • the second active ingredient should be different from the second active ingredient for wound healing.
  • wound healing encompasses physiological processes for the regeneration of a destroyed skin tissue (epidermis, dermis), which cause the closure of a wound, in particular by new formation of connective tissue or capillaries.
  • a distinction is made between primary wound healing with rapid, uncomplicated closure in Sequence of minimal connective tissue regeneration between well perfused, if necessary, adapted wound margins of a clean wound, and secondary wound healing with delayed wound healing as a result of non - excludable bacterial inflammation in wounds with a variety of wound edges, or wound infection with filling of the tissue defect with granulation tissue and extensive scarring as well as epithelization of Edge ago.
  • the phases of wound healing namely the latency phase with leakage of fluid and scab formation in the first hours as well as a receptive phase with catabolic autolysis with degradation of damaged tissue.
  • the proliferation phase or granulation phase takes place with anabolic repair to form collagen by connective tissue cells (fibroblasts), and finally a reparation phase with Transformation of granulation tissue into scar tissue.
  • the active ingredients for wound healing are able to support wound healing, if necessary to support the aforementioned phases, and to avoid complications at and in the wound.
  • an applicator system is one such system that includes a device that causes the microneedle array to be administered to the skin for delivery of the active ingredients and that the first and second wound healing agents are intradermally applied.
  • the applicator system may comprise a triggering device which is controlled electrically or mechanically.
  • the applicator system may include a plunger which applies or applies the microneedle array to the skin so that the microneedles penetrate into the skin.
  • the triggering device may comprise, for example, a pump, a syringe or a spring, so that a piston stroke can take place with sufficient energy.
  • the plunger may be of any shape and nature and is primarily intended to provide the microneedle array from a first position to a second position for delivery of the active ingredients to the skin.
  • the applicator system may further include a push button or thread. Furthermore, the applicator system can be designed in such a way that the first active substance is released, for example by opening an active substance reservoir.
  • the microneedle array may include a plurality of microneedles for delivering a substance across the skin or into the skin of a patient, with the microneedle array applied to the skin of the patient.
  • Each of the microneedles of the microneedle array preferably has an elongated shaft with two ends, one end of the shaft being the base of the microneedle with which the microneedle is attached to the planar support or with which the microneedle is integrated into the planar support.
  • the base of the opposite end of the shaft is preferably designed tapered to allow the easiest possible penetration of the microneedle into the skin.
  • Each hollow microneedle has at least one passage or channel or at least one bore extending from the Base of the microneedle extends to the tip of the microneedle or almost to the tip of the microneedle.
  • the passages preferably have a round diameter.
  • the microneedles can be made of different materials and consist of, for example, a metal, a ceramic material, a semiconductor, an organic material, a polymer or a composite, which may be solid or partially solid or hollow.
  • Preferred materials for producing such microneedles are, for example
  • the polymers may particularly preferably be biodegradable polymers or water-soluble polymers, in particular of biological or non-biological origin, preferably polymers, such as alpha-hydroxy acids, such as lactic acid and / or glycolic acid, polylactides, polyglycolides, polylactide-co-glycolides, and copolymers with polyethylene glycol, polyanhydrides,
  • Poly (ortho) esters polyurethanes, polybutyric acids, polyvaleric acids, and polylactide-co-caprolactones.
  • the polymers may likewise be non-biodegradable polymers, for example from the group of polycarbonates, polyesters,
  • the microneedles consist of a monocrystalline material, for example of monocrystalline silicon.
  • the microneedles may have a shaft with a round cross-section or a non-round cross-section, for example with a triangular, quadrangular or a polygonal cross-section.
  • the shaft may have one or more passages that extend from the needle base to the needle tip or approximately to the needle tip.
  • the microneedles may be formed as (counter) hooks, with one or more of these microneedles having one or more such hooks.
  • the microneedles can be designed helically and rotatably arranged, thereby facilitating the penetration into the skin when applying a rotating movement and effecting an anchoring in the skin (DE 103 53 629 A1), in particular at the desired penetration depth in the epidermis.
  • the diameter of a microneedle is usually between 1 ⁇ and 1000 ⁇ , preferably between 10 ⁇ and 100 ⁇ .
  • the diameter of a passage is usually between 3 ⁇ and 80 ⁇ and is suitable for the passage of preferably liquid substances, solutions and fabric preparations.
  • the length of a microneedle is usually between 5 ⁇ and 6,000 ⁇ , in particular between 100 ⁇ and 700 ⁇ .
  • the microneedles are attached with their base to a flat carrier or integrated into a flat carrier.
  • the microneedles are preferably arranged substantially perpendicular to the surface of the carrier standing.
  • the microneedles can be arranged regularly or irregularly.
  • An array of multiple microneedles may comprise microneedles having different cross-sectional shapes, different sized diameters and / or different lengths.
  • the array of multiple microneedles may comprise only hollow microneedles.
  • the assembly may also comprise solid microneedles, as well as semi-solid composites, such as solid micro-needles interspersed with fluid inclusions.
  • the density of the microneedles on a support is 5 - 5,000 pieces / cm 2 , in particular 5 - 1,000 pieces / cm 2 .
  • high densities of the microneedles can impair wound healing.
  • the microneedle array may comprise a planar carrier, wherein the carrier has a substantially disc-shaped, plate-shaped or foil-like basic shape.
  • the carrier may have a round, oval, triangular, square or polygonal base.
  • the carrier may be made of different materials, for example, a metal, a ceramic, a semiconductor, an organic material, a polymer or a composite.
  • materials which are suitable for the preparation of the carrier may preferably be mentioned films or sheet-like materials, for example microporous membranes, preferably of polyethylene (PE) or polypropylene (PP), or diffusion membranes, preferably of ethylene-vinyl acetate copolymer (EVA ) or polyurethane (PUR).
  • PE polyethylene
  • PP polypropylene
  • EVA ethylene-vinyl acetate copolymer
  • PUR polyurethane
  • Suitable materials for the preparation of the carrier may be selected from the group comprising polyesters such as polyethylene terephthalates (PET), polycarbonates (PC), polyether ketones (PAEK), polyethylene naphthalate (PEN), polybutylene terephthalate (PBT), polyurethanes (PU), polystyrenes (PS), Polyamides (PA), polyoxymethylene (POM), polyolefins such as polyethylene (PE) and polypropylene (PP), polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), polylactate (PLA), polymethyl methacrylate (PMMA) and cellulosic based plastics such as cellulose hydrate or cellulose acetate.
  • Suitable materials for the preparation of the support can also be selected from the group of metals comprising aluminum, iron, copper, gold, silver, platinum, alloys of the aforementioned metals and other pharmaceutically acceptable metal foils or metallized films
  • the carrier is made of a flexible material, such as a plastic.
  • a wearer of a flexible material can better conform to the skin surface and its curvature than a wearer of a non-flexible material. This achieves better contact of the microneedle array with the skin, thereby improving the reliability of the microneedle array.
  • the microneedle array is a planar or planar microneedle array.
  • microneedle array is at least wetted with an active ingredient for wound healing or, preferably, an active ingredient for wound healing is contained.
  • the active ingredient for wound healing can be integrated or incorporated in a preferred embodiment into the matrix of the microarray. Furthermore, in a preferred embodiment, the active ingredient may be applied to the wound needles on the microneedles or on the support.
  • the tip of at least one microneedle wets with a wound healing agent, or a wound healing agent is contained in the tip of at least one microneedle.
  • the active ingredient for wound healing may be contained on and / or in the microneedle array and / or carrier in an amount of 0.01-200 mg / cm 2 .
  • the applicator system comprising a microneedle array can be configured with conventional functional objects which allow fixation on the skin, as well as allow easy handling for pressure exertion on the skin and in particular can contain at least one fixative.
  • the applicator system comprising a microneedle array can have at least one reservoir which contains at least one arbitrary substance, in particular a first active ingredient or drug, preferably in the form of a solution or preparation.
  • the reservoir serves to store at least any drug or drug contained in the system.
  • the reservoir communicates with the passages of the hollow microneedles such that there is a fluid connection between the reservoir and the passages of the microneedles communicating with the reservoir.
  • the contents of the reservoir can be released from the micro needle system via the passages of the microneedles out of the reservoir when pressure is exerted on the reservoir after application of the microneedle system to the skin of a patient.
  • the stock preparation exits at or near the tips of the microneedles from the microneedle system and can penetrate into the target tissue.
  • the reservoir is attached to a surface of the sheet carrier, namely, the surface of the carrier opposite the surface of the carrier from which the microneedles protrude.
  • the reservoir is easily compressible to provide little resistance to the pressure applied to the reservoir, and thus to be able to pass the pressure on the preparation contained in the reservoir to escape.
  • the reservoir may be in the form of a flexible bag.
  • the reservoir is designed as a cushion or balloon and made of an elastic material, for example of an elastomeric polymer or rubber.
  • polymers are polyesters such as polyethylene terephthalates (PET), polycarbonates (PC), polyether ketones (PAEK), polyethylene naphthalate (PEN), polybutylene terephthalate (PBT), the polyurethanes (PU), polystyrenes (PS), polyamides (PA), polyoxymethylene (POM ), Polyolefins such as polyethylene (PE) and polypropylene (PP), polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC). Polylactate (PLA), and cellulosic based plastics such as cellulose hydrate or cellulose acetate.
  • the microneedle system comprising a microneedle array is configured with an applicator.
  • applicators advantageously permit the activation of a pressure mechanism for penetrating the microneedle array into the skin or stratum corneum (see for example WO2008091602A2, WO2016162449 AI).
  • the microneedle array may contain fixing means, which are preferably fixed to the skin of a patient or test persons with the aid of a pressure-sensitive adhesive strip or plaster.
  • pressure-sensitive adhesives are highly viscous substances that stick to the skin after a short light pressure, so-called pressure-sensitive adhesives (PSA). They have high cohesive and adhesive forces.
  • PSA pressure-sensitive adhesives
  • the fixing means may consist of a band, elastic band, rubber or belt. Such fixatives can be used to secure attachment to the body.
  • the invention therefore relates to an applicator system according to the invention containing a microneedle array for intradermal administration, which has fixing agents for the skin.
  • intradermal application (synonym:” intracutaneous application ) describes according to the invention the administration of any active ingredients via the microneedle array into the skin and requires puncturing or penetration of the microneedles into the skin.
  • the invention also relates to a method for intradermal administration, wherein at least a first active ingredient is applied to a carrier by means of an applicator system comprising a microneedle array having a plurality of microneedles, the microneedles and / or the carrier containing at least one second wound healing agent.
  • Example 1 a. ) Experimental Design
  • microarray without dexpanthenol and one microarray with 150 mg dexpanthenol are applied to healthy skin (forearm) manually, fixed with tape and removed after one hour of wearing. For comparison, the application site is photographed prior to attachment of the microarrays, immediately after acceptance of the microarrays without wiping off any residues and after 70 hours. b. ) Material and methods
  • the skin treated with microarray without dexpanthenol is reddened and injured in some places.
  • the microarray treated with dexpanthenol skin is less red. Injuries are not visible to the naked eye. d. )

Landscapes

  • Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Hematology (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne un système d'application contenant une matrice de micro-aiguilles et son utilisation pour administration intradermique de principes actifs, en particulier des médicaments, ladite matrice de micro-aiguilles se prêtant à la pénétration cutanée chez l'homme ou l'animal et comprenant au moins un principe actif pour la cicatrisation.
EP18759262.1A 2017-08-04 2018-08-04 Système d'application contenant une matrice de micro-aiguilles présentant un principe actif pour la cicatrisation Pending EP3661586A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102017117784.1A DE102017117784A1 (de) 2017-08-04 2017-08-04 Applikatorsystem enthaltend ein Mikronadelarray aufweisend einen Wirkstoff für die Wundheilung
PCT/EP2018/071209 WO2019025625A1 (fr) 2017-08-04 2018-08-04 Système d'application contenant une matrice de micro-aiguilles présentant un principe actif pour la cicatrisation

Publications (1)

Publication Number Publication Date
EP3661586A1 true EP3661586A1 (fr) 2020-06-10

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP18759262.1A Pending EP3661586A1 (fr) 2017-08-04 2018-08-04 Système d'application contenant une matrice de micro-aiguilles présentant un principe actif pour la cicatrisation

Country Status (12)

Country Link
US (1) US20200188649A1 (fr)
EP (1) EP3661586A1 (fr)
JP (2) JP2020529269A (fr)
KR (1) KR20200037834A (fr)
CN (1) CN111212674A (fr)
AU (1) AU2018311234A1 (fr)
BR (1) BR112020001778A2 (fr)
CA (1) CA3071052A1 (fr)
DE (1) DE102017117784A1 (fr)
MX (1) MX2020001310A (fr)
RU (1) RU2020108160A (fr)
WO (1) WO2019025625A1 (fr)

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WO2021183626A1 (fr) 2020-03-10 2021-09-16 University Of Connecticut Bandage thérapeutique
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KR20200037834A (ko) 2020-04-09
CN111212674A (zh) 2020-05-29
CA3071052A1 (fr) 2019-02-07
JP2020529269A (ja) 2020-10-08
US20200188649A1 (en) 2020-06-18
JP2023130489A (ja) 2023-09-20
RU2020108160A (ru) 2021-09-07
RU2020108160A3 (fr) 2021-11-02
AU2018311234A1 (en) 2020-03-19
MX2020001310A (es) 2020-03-20
DE102017117784A1 (de) 2019-02-07
WO2019025625A1 (fr) 2019-02-07

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